The Morris K. Udall Parkinson's Disease Center of Excellence at Emory University will be a highly collaborative research program in which electrophysiologists, pharmacologists, and anatomists work together to study the effects of existing and new treatments for parkinsonism from a circuit perspective. The Center draws upon the proven ability of the basal ganglia research community at Emory to conduct translational research. Other Center assets will be its close ties to the clinical movement disorders group at Emory, the fact that a portion of the research will be carried out in primates at the Yerkes National Primate Research Center, and the Center's connection to an active population of patients with Parkinson's disease in the Atlanta area. Emory University is strongly committed to Parkinson's Disease research, and will support the Center by funding pilot grants and an invited speaker seminar series. The center will consist of four projects and two cores. Project 1 (Dr. Jaeger) will examine changes imposed by altered basal ganglia input onto thalamic neurons in the parkinsonian state. Project 2 (Dr. Wichmann) is a series of experiments in parkinsonian primates to compare the thalamic effects of pallidal and subthalamic nucleus inactivation and stimulation, as are commonly used to treat advanced parkinsonism in patients, with the goal of identifying changes in thalamic activity that are associated with the antiparkinsonian effects of these procedures. Project 3 (Dr. Miller) is a series of translational experiments that examine the use of orally active TrkB receptor agonists as symptomatic or neurorestorative treatment for Parkinson's disease in different rodent and primate models. Project 4 (Dr. Conn, Vanderbilt), investigates the effects of a series of novel subtype-selective muscarinic acetylcholine receptor antagonists and activators on basal ganglia activity, and on parkinsonism in rodent models. The projects will be supported by an administrative core (Core A, Dr. Wichmann, PI; Dr. DeLong, Co-1, Dr. Pearson, administrator), and by an anatomy and behavior core (Core B, Dr. Smith) which will provide immunohistochemistry and electron microscopy services to all of the center projects, and will conduct behavioral testing in MPTP-treated monkeys under project 3.